Major depressive disorder (MDD) is a highly heterogeneous diagnosis wherein the nine MDD criterion signs and symptoms reflect 256 unique symptom combinations.1 Accordingly, MDD comprises a broad set of phenotypes observed across clinical practice, including primary care. With intensifying global efforts to prevent male suicide, attention has rapidly focused on better understanding men’s experiences of MDD. Pertinent to these efforts is the operationalization of MDD, which is characterized by the two cardinal symptoms of depressed mood and anhedonia (the loss of interest or pleasure in all, or nearly all, activities for most of the day nearly every day). However, debate remains regarding the adequacy of this conceptualization of depression as applied to men socialized within dominant discourses of masculinity that prohibit men acknowledging or seeking help for depression.2–4 DSM-5-TR SEX AND GENDER CONSIDERATIONS FOR MDD The text revision of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) offers a noteworthy change to the sex and gender considerations for MDD. While the nine diagnostic criteria for an MDD diagnosis have remained unchanged relative to the preceding DSM-5 text (because the purpose of DSM’s text revision version is to update the text, not change diagnostic criteria), an important new phenomenological statement has been added. Whereas DSM-5 offered no guidance related to associated gendered symptom expression apart from commenting on the epidemiology and gender paradox of suicide attempts (higher among females) and suicide deaths (higher among males), DSM-5-TR offers the following: There is some evidence for sex and gender differences in phenomenology and course of illness. Women tend to experience more disturbances in appetite and sleep, including atypical features such as hyperphagia and hypersomnia, and are more likely to experience interpersonal sensitivity and gastrointestinal symptoms. Men with depression, however, may be more likely than depressed women to report greater frequencies and intensities of maladaptive self-coping and problem-solving strategies, including alcohol or other drug misuse, risk taking, and poor impulse control.5(p 190) In general, women are more likely to internalize (e.g., withdraw, cry), and men are more likely to externalize (e.g., display anger, utilize alcohol to cope).6 Naturally, this has prompted the consideration of a biological basis for differences. Yet, compelling evidence of biological differences underpinning men’s depression symptoms and their maladaptive self-coping and problem-solving strategies remains scarce.7 Regarding neuroimaging, recent analyses from the ENIGMA MDD consortium (inclusive of >4300 MDD patients across 45 study cohorts) reported no diagnosis × sex interaction effects, indicating that structural brain alterations are unlikely to contribute to sex differences in MDD symptoms.8 In relation to sex hormones, again, the evidence is inconclusive, although lower estrogen levels in women may reduce sleep quality and thus elevate the risk of MDD.9 By contrast, testosterone is often referenced as a protective factor for the onset on prototypical depression symptoms in men,10 although some argue that testosterone levels above, or below, normal levels may contribute to depression and suicide risk in men.11 A recent meta-analysis showed that relationships across baseline, dynamic, and manipulated testosterone levels with men’s aggression were weak (e.g., r’s ≤ .17).12 A separate meta-analysis has indicated, however, that testosterone treatment may be a useful approach to managing MDD in men.13 Overall, sex differences in MDD symptoms (and co-occurring symptoms) therefore occur due to a complex interactive matrix of social and physiological factors.10 As we discuss below, men’s adherence to masculine norms serves as a promising social explanation for these differences in primary MDD and co-occurring symptoms. The revised text in DSM-5-TR is important for a range of reasons. Notably, it reflects the efforts of researchers over recent decades who have sought to better understand and document (and by extension, treat) men’s experiences of major depression. This work dates back to the foundational Swedish Gotland studies in the 1990s, where the term male depression syndrome originated,14 and extends to work published in this journal.15 More importantly, though, the recognition of sex and gender considerations in DSM-5-TR formally notes what many mental health clinicians working directly with men have long suggested—namely, that major (unipolar) depression does not always manifest as low mood.16 While this may at first seem contrary to the construct of MDD as characterized by the two cardinal symptoms of depressed mood and anhedonia, below we highlight existing challenges within the MDD diagnostic criteria that bear this out. Men experiencing depression tend to report a constellation of signs and symptoms beyond those covered by current diagnostic criteria. Research has shown these to include externalizing symptoms such as irritability, anger, substance misuse, risk taking, impulsivity, and overinvolvement in work, which confer higher risk of suicide.3 These additional signs and symptoms complicate initial diagnosis, impede treatment access, and, ultimately, can compromise recovery. Conceptually, it is here that the interrelationship between depressive psychopathology, signs, symptoms, and co-occurring symptoms is key. SIGNS, SYMPTOMS, AND CO-OCCURRING SYMPTOMS As articulated by King,17signs of a disease or disorder signal an objective indicator of underlying disease or pathology. The presence and expression of these dictate whether a diagnosis is made via the clinical judgment of a health professional, consistent with established diagnostic criteria. By contrast, illness symptoms represent the lived and subjective “complaints” that the patient experiences. They may, or may not, contribute to diagnostic decision making. As the expression suggests, co-occurring symptoms frequently accompany such signs and symptoms (or disorders). Unfortunately, the boundaries between signs, symptoms, and co-occurring symptoms can be unclear in relation to MDD specifically and mental health more broadly. Unlike diseases where pathophysiology (e.g., biomarker-based indicators) directs diagnosis through objective measurement or assessment, many aspects of mental disorders cannot be objectively observed. In such instances, the “symptom” (as subjectively reported by the patient) needs to additionally be considered a “sign” that is, in turn, diagnostic. While this makes sense at face value, DSM-5-TR fails to define how it conceptualizes the interaction between signs and symptoms (which is unfortunate for a wide range of disorder definitions). Clinicians are therefore left to assume a definition consistent with that offered by King,17 as per above. We note, however, that many nonpsychiatric medical diagnoses, such as migraine headache, are unable to be objectively observed. EXTERNALIZING SYMPTOMS The language used by DSM-5-TR in characterizing co-occurring MDD symptoms among men (e.g., maladaptive self-coping and problem-solving strategies, alcohol or other drug misuse, risk taking, and poor impulse control) can be broadly grouped under the label of externalizing symptoms. Not all men (or indeed, women) with MDD experience co-occurring externalizing symptoms, but some do.18 Equally so, not all individuals with MDD experience psychomotor disturbance, but some do—estimated to be 20% of cases.19 Hence, just as psychomotor disturbance is experienced in proportionally few cases of MDD, an externalizing profile may also be experienced in a minority of MDD diagnoses among men. Zajac and colleagues20 recently grouped symptom profiles of 1000 Canadian men from the general population, matched to census data on age and location. Four distinct cohorts were identified in the sample: those classified as not depressed (69%); those with DSM-5–congruent prototypical MDD symptoms of at least mild severity (8%); those with a mixed prototypical and externalizing (e.g., anger, aggression, substance misuse, risk taking) profile (12%); and those experiencing externalizing symptoms only (11%). For all symptomatic groups, risk of mental illness was significantly elevated. Of note, however, relative to the non-depressed group, men experiencing only externalizing symptoms and those with mixed prototypic/externalizing symptomology were at significantly increased risk of suicide. More recent work has further confirmed the presence of distinct groups of depressed men with heightened risk of suicide.21 Hence, externalizing depression symptoms may offer prognostic value in predicting current suicide risk for men over and above that provided via standardized screening tools (e.g., the Patient Health Questionnaire [PHQ-9]) for assessing MDD symptoms. Using data from the U.S. National Comorbidity Survey Replication, Martin and colleagues2 reported that men relative to women (p’s < .001) were more likely to endorse anger attacks/aggression (94.9% vs. 88.9%), substance misuse (61.4% vs. 40.6%), and risk-taking behavior (52.7% vs. 29.1%). Women relative to men were more likely to endorse stress (75.2% vs. 63.3%; p < .001), irritability (94.7% vs. 86.6%; p < .001), sleep problems (47.1% vs. 29.2%; p < .001), and anhedonia (91.8% vs. 87.8%; p < .05). Arguments that men may display an externalizing MDD phenotype are nonetheless contested,22 and the onus remains on researchers to implement high-quality study designs and measurement tools that can rigorously provide empirical weight to advance the field in relation to further refinement of diagnostic criteria. Validated male-specific depression screening tools are now available for use in research and clinical practice to assess for so-called male depression symptoms.3 The most rigorously validated of these is the Male Depression Risk Scale (MDRS-22),4 a 22-item measure assessing six symptoms domains. Four of these domains focus on externalizing symptoms (anger and aggression; alcohol use; drug use; risk taking), with the remaining two assessing men’s experiences of depressed mood (emotion suppression, somatic symptoms). The MDRS-22 demonstrates good sensitivity in detecting past four-week suicide attempts in men (area under the curve = 0.837; 95% confidence interval, 0.721–0.954), and the established cutoff criterion identifies proportionally more cases of men with suicide ideation than the “moderate depression” cutoff on the widely used measure of prototypic MDD symptoms, the PHQ-9.4 Of note, a brief, seven-item version of the MDRS is now available,21 with included items closely aligning with the co-occurring externalizing MDD symptoms identified in DSM-5-TR (see Table 1).23 We argue that adjunctive use of brief measures like the MDRS-721 should sit alongside routine use of established prototypic MDD symptom screens (e.g., PHQ-9) in primary care and mental health settings with men. As identified by Zajac and colleagues,20 this approach has the potential to identify a subgroup of men (~11%) who rate as subthreshold on MDD symptoms assessed by the PHQ-9 but who screen positive for externalizing symptoms on the MDRS-7 and are at increased risk of suicide. Table 1. - Items from the Male Depression Risk Scale Short Form (MDRS-7) Please think back over the last month and respond to each item considering how often it applied to you. Please respond where 0 = not at all; 4 = all the time. Not at all A little of the time Some of the time Most of the time All of the time 1. I bottled up my negative feelings 0 1 2 3 4 2. I had unexplained aches and pains 0 1 2 3 4 3. I needed alcohol to help me unwind 0 1 2 3 4 4. I overreacted to situations with aggressive behaviour 0 1 2 3 4 5. I stopped caring about the consequences of my actions 0 1 2 3 4 6. It was difficult to manage my anger 0 1 2 3 4 7. Using drugs provided temporary relief 0 1 2 3 4 Note. MDRS items are reprinted from Rice et al. (2020)23 under Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). For information on MDRS-7 scoring, see Herreen et al. (2022).21 IRRITABILITY AND MDD MDD criteria listed in DSM-5-TR (and indeed, earlier DSM versions) include a commonly exhibited externalizing symptom—namely, irritability—albeit with a developmental qualifier. The two core MDD symptoms that must be present to be eligible for a diagnosis are (1) depressed mood (“Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad, empty, hopeless) or observation made by others [e.g., appears tearful]”), and (2) anhedonia (“Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day [as indicated by either subjective account or observation]”). However, the depressed mood criterion provides a developmental caveat, which reads as follows: “Note: In children and adolescents, can be irritable mood.” Unfortunately, DSM-5-TR fails to offer any guidance as to why irritable mood should replace depressed mood in patients <18 years; based on recent studies, irritable mood remains an important indicator of underlying psychological distress in adult men.24–27 The developmental caveat for individuals <18 years may relate to difficulties in verbal expression of affective states (i.e., experiences of low mood) and subsequent frustration expressed as irritation or anger in children and adolescents—with the background assumption that, by extension, such difficulties resolve in adulthood. The developmental exclusion of adult irritability as a criterion MDD symptom has long been critiqued and criticized.28 For example, evidence supports the notion that “anger attacks” (analogous to panic attacks) are common among individuals with MDD, especially men.29 It is strangely unclear why the symptom of irritability can supersede depressed mood for those <18 years, but not adults. We acknowledge, along with others,30 that irritable mood features across a range of DSM-5-TR diagnoses (including bipolar disorders). The growing concern, however, is that the construct of irritability and its assessment is so poorly understood, researched, and defined that its inclusion in diagnostic criteria for any disorder is highly questionable.30 Consistent with Fava and Rosenbaum,29 however, our view is that (1) irritable mood does offer diagnostic utility and frequently confers functional (especially relational) impairment in affected individuals, and (2) spontaneous deactivation of irritability is unlikely to occur for those affected who would otherwise qualify for an MDD diagnosis <18 years but who would no longer qualify at age 18. Resolution of this matter will be important in the future development of DSM-6, given that it may drastically improve identification of underlying mood disorders in males. EXTERNALIZING SYMPTOMS AND BIPOLAR II DISORDER An alternative consideration worthy of further research is the conceptual overlap between the constellation of externalizing symptoms referred to in DSM-5-TR and the presence of an underlying bipolar disorder (in particular, bipolar II disorder). Overlap in diagnostic criteria for irritable mood as part of a hypomanic episode is most salient here. However, irritability in the context of hypomania needs to occur in the context of persistently increased activity or energy (lasting at least four consecutive days but less than seven days) in the presence of at least three other bipolar II criterion symptoms. Whereas bipolar I disorder is characterized by a threshold manic episode typically so severe that it is obvious and evident to others (thus typically prompting assertive intervention, including emergency services), bipolar II disorder is more likely to exist undetected.31 Clear reference is made in DSM-5-TR to differential diagnostic features between MDD, bipolar I, and bipolar II. More research is needed, however, to clarify and distinguish co-occurring MDD externalizing symptoms and criterion symptoms of bipolar II. It may be that the men experiencing an externalizing depression phenotype are prodromal for later onset of bipolar II disorder. This issue is noteworthy and important to clarify because evidence-based treatment, especially pharmacotherapy (e.g., prescription of selective serotonin reuptake inhibitors versus mood stabilizers), is very different for unipolar versus bipolar depressive disorders. CULTURE AND MASCULINITY We also note that the preamble to the DSM-5-TR5 offers an important cautionary note regarding the impact of cultural norms and diagnostic practices: To accurately assess potential signs and symptoms of psychopathology, clinicians should routinely consider the impact of cultural meanings, identities, and practices on the causes and course of illness for example, through any of the following factors: . . . social stigma.5(p 16) This statement has particular relevance and significance in relation to men’s depression. While international campaigns, such as those led by the men’s health charity Movember, are seeking to educate men regarding MDD (including normalizing help seeking), socialized masculine norms continue to affect men’s experience and expression of MDD, along with clinicians’ efforts to identify it in men. In their systematic review of 37 studies, Seidler and colleagues32 found that conformity to traditional masculine norms exerted a threefold effect on men experiencing depression, influencing (1) men’s symptoms and expression of symptoms (including the expression of externalizing symptoms), (2) men’s attitudes, intentions, and behaviors regarding help seeking, and (3) men’s symptom management. Here, conformity to masculine norms can be viewed as an important cultural factor relevant to men’s experience and expression of depression. This is consistent with meta-analytic findings15 and rigorous population-based research2 highlighting the salience of externalizing symptoms among men. New initiatives are seeking to be better attuned to men’s gendered experience of depression, including the tailored and the Men in AND As in men experiencing depressed mood may also report co-occurring externalizing symptoms (e.g., alcohol or other drug misuse, risk taking, and poor impulse of alcohol or drug misuse, risk taking, and poor impulse can be assessed subjectively (e.g., at the of subjective symptoms) and objectively (e.g., at the of diagnostic especially via from including and As further evidence it will through of data and from clinical criteria for MDD as applied to men’s depression will further The with researchers to provide compelling evidence that supports (or the that externalizing symptoms (or should be included within MDD diagnostic criteria for adults. We therefore for a global research to this should be given to brief screening for male depression symptoms (e.g., the as part of medical in primary care settings and a of externalizing symptoms within diagnostic criteria for adult MDD via of the developmental age caveat for irritability, or through additional symptom is likely The construct of externalizing depression symptoms will now that DSM-5-TR makes reference to as frequently co-occurring with MDD for men. DSM-5-TR also notes two relevant for further (1) depressive with hypomania least two days but less than four and (2) behavior disorder (which is an identified of further study in than a disorder per There is value in conceptual related to these as men’s depression research A further that has been in relation to men’s mental health is research the salient of in men’s and that particular symptoms (or including panic and of of are more likely to be experienced by between men’s experiences of MDD, and externalizing symptoms may be a useful of future The growing research and clinical interest in men’s depression is and needed, as i
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